The IgE-mediated secretory response of sensitized basophils or mast cells to appropriate antigen is the initiating event of immediate hypersensitivity reactions. It is now recognized that the variety of mediators released during this process induce development of a localized inflammatory response. These inflammatory events are responsible for the amplification of allergic reactions and, if potentiated or prolonged, the development of allergic disease states. Therefore, elucidation of the mechanisms for the amplification or prolongation of allergic reactions is important to an understanding of the pathogenesis of atopic disease. A potentially important mechanism is potentiation or prolongation of basophil and mast cell secretory processes by reactants generated during the inflammatory events. Using human basophils, three potential influences on the secretory process have been identified. (1) Complexed or surface-bound IgG potentiates IgE-mediated histamine release. (2) Major basic protein isolated from human eosinophil granule stimulates IgE-independent histamine release. (3) The model basic polypeptide protamine potentiates IgE-mediated histamine release. It is postulated that similar interactions in vivo may constitute important mechanisms for the amplification and prolongation of allergic reactions involving human basophils. The project has four goals. (1) Establish the participation of basophil Fc(IgG) receptors and basophil 5-lipoxygenase metabolites in the enhancement mechanism by complexed or surface-bound IgG. (2) Determine the mechanism and binding moiety for major basic protein-stimulated histamine release. (3) Determine the mechanism for enhancement by basic polypeptides and identify basic polypeptides associated with allergic and inflammatory reactions that may potentiate IgE-mediated release. (4) Extend the above influences to the release of additional basophil mediators, particularly lipoxygenase and cyclo-oxygenase products.